Nanoparticles developed at UMass Medical
School advance potential clinical application for photodynamic therapy

By Jim Fessenden

UMass Medical School Communications

October 15, 2014

Research by Gang Han, PhD, shows
that upconversion nanoparticles that can convert near-infrared light into red
light can be used to extend photodynamic therapy for some cancers found in
deeper tissues.

Research by Gang Han, PhD, shows
that upconversion nanoparticles that can convert near-infrared light into red
light can be used to extend photodynamic therapy for some cancers found in
deeper tissues.

An international group of scientists led
by Gang Han, PhD, has combined a new type of nanoparticle with an FDA-approved
photodynamic therapy to effectively kill deep-set cancer cells in vivo with
minimal damage to surrounding tissue and fewer side effects than chemotherapy.
This promising new treatment strategy could expand the current use of
photodynamic therapies to access deep-set cancer tumors.

“We are very excited at the potential
for clinical practice using our enhanced red-emission nanoparticles combined
with FDA-approved photodynamic drug therapy to kill malignant cells in deeper
tumors,” said Dr. Han, lead author of the study and assistant professor of
biochemistry & molecular pharmacology. “We have been able to do this with
biocompatible low-power, deep-tissue-penetrating 980-nm near-infrared light.”

In photodynamic therapy, also known as
PDT, the patient is given a non-toxic light-sensitive drug, which is absorbed by
all the body’s cells, including the cancerous ones. Red laser lights
specifically tuned to the drug molecules are then selectively turned on the
tumor area. When the red light interacts with the photosensitive drug, it
produces a highly reactive form of oxygen (singlet oxygen) that kills the
malignant cancer cells while leaving most neighboring cells unharmed.

Because of the limited ability of the
red light to penetrate tissue, however, current photodynamic therapies are only
used for skin cancer or lesions in very shallow tissue. The ability to reach
deeper set cancer cells could extend the use of photodynamic therapies.

In research published online by the
journal ACS Nano of the American Chemical Society, Han and colleagues describe a
novel strategy that makes use of a new class of upconverting nanoparticles
(UCNPs), a billionth of a meter in size, which can act as a kind of relay
station. These UCNPs are administered along with the photodynamic drug and
convert deep penetrating near-infrared light into the visible red light that is
needed in photodynamic therapies to activate the cancer-killing drug.

To achieve this light conversion, Han
and colleagues engineered a UCNP to have better emissions in the red part of the
spectrum by coating the nanoparticles with calcium fluoride and increasing the
doping of the nanoparticles with ytterbium.

In their experiments, the researchers
used the low-cost, FDA-approved photosensitizer drug aminolevulinic acid and
combined it with the augmented red-emission UCNPs they had developed.
Near-infrared light was then turned on the tumor location. Han and colleagues
showed that the UCNPs successfully converted the near-infrared light into red
light and activated the photodynamic drug at levels deeper than can be currently
achieved with photodynamic therapy methods. Performed in both in vitro and with
animal models, the combination therapy showed an improved destruction of the
cancerous tumor using lower laser power.

Yong Zhang, PhD, chair professor of
National University of Singapore and a leader in the development and application
of upconversion nanoparticles, who was not involved in the study, said that by
successfully engineering amplified red emissions in these nanoparticles, the
research team has created the deepest-ever photodynamic therapy using an
FDA-approved drug.

“This therapy has great promise as a
noninvasive killer for malignant tumors that are beyond 1 cm in depth—breast
cancer, lung cancer and colon cancer, for example—without the side-effects of
chemotherapy,” Dr. Zhang said.

Han said, “This approach is an exciting
new development for cancer treatment that is both effective and nontoxic, and it
also opens up new opportunities for using the augmented red-emission
nanoparticles in other photonic and biophotonic applications.”